Integrated micro-pump and electro-spray

ABSTRACT

Disclosed is a micro-pump having at least one channel on a substrate where the channel has an inlet and an outlet. The micro-pump includes a first and second electrode coupled to the substrate, wherein the electrodes deliver a current that produces an electric field across the substrate to create a flow from the inlet to the outlet of a fluid contained in the channel. The micro-pump also includes an ion-specific membrane housing for the electrode reservoir minimizes bubble generation, fluid leakage and pressure loss. Further, at least a portion of the channel contains a chemically formed porous matrix.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 60/655,437, entitled “Integrated DC pump/electro-spray,” filed onFeb. 24, 2005, and PCT Application No. PCT/US06/06457, entitled“Integrated Micro-Pump and Electro-Spray,” filed on Feb. 24, 2006, bothof which are hereby incorporated by reference in their entireties.

GOVERNMENT INTEREST STATEMENT

The United States Government has rights in this invention pursuant toContract No. DAAB 07-03-3-K414 with the United States Army.

FIELD OF THE DISCLOSURE

This disclosure relates generally to micro-fluidic pumping and sprayingdevices, and, more particularly, to an integrated DC micro-pump andelectro-spray and methods for manufacturing the same.

BACKGROUND

A Total Analytical System (TAS) is a chemical analysis system thatautomates all necessary steps for analysis of a chemical substance (e.g.sampling, transport, filtration, dilution, chemical reactions,separation and detection). Considerable effort in analytical chemistryhas been directed toward the miniaturization of these systems to enablerapid, portable, and automated analyses of small-volume samples.Ideally, a micro-TAS (t-TAS) integrates all function units necessary toanalyze a chemical sample on a single micro-fluidic substrate, sometimesreferred to as a “lab-on-a-chip.” Because the flow velocity in amicro-channel scales as the channel radius squared, scaling down thesystem by a factor of n requires an n² increase in the driving pressureto maintain the same velocity. As such, a notable component of a μ-TASis a powerful micro-fluidic pump capable of generating high pressure.Moreover, this pump may be integrated into the entire system on the samesubstrate because fluid transfer from an external pump may defeat manyof the advantages of μ-TAS and may require tedious tubing connection foreach run. Constant high-pressure but low flow rates for micro- andnano-liter samples and especially pulsation-free flows are often theprimary pump requirements for micro-flow injection analysis (μ-FIA),micro-column liquid chromatography (P-LC), and other t-TAS.

One micro-pump that has been proposed for use with μ-TAS is theelectroosmotic pump (EOP), which uses electric current to cause a bulkfluid movement through a system. EOPs typically suffer from severalmajor problems. One possible problem is that, with open channel orcapillary EOPs, there is a low stall pressure and, therefore, these EOPsare generally not used in systems with high-pressure loads.High-pressure build-up can be achieved if the pump channel is smaller orif a dense packing material is used to produce large hydrodynamicresistance. Unlike mechanical pumps, which generate a local highpressure and for which hydrodynamic resistance in the pump would reducethis driving pressure, pure electroosmotic flow does not produce apressure field, but instead relies on hydrodynamic resistance to reducethe flow and build a high pressure along the pump channel. Hence, in acounter-intuitive manner, EOP pump channels need to be as small aspossible. However, a single pump channel cannot produce enough flow anda large bundle of small micro-channels is needed for the EOP.

Another potential problem is electrolytic bubble generation, because ofthe large current in the open channel. In aqueous solutions, when theapplied electrode potential exceeds a threshold approximately 1.1 V,significant electrolysis and other electrode reactions may occur,producing ions that contaminate the sample and generate bubbles, whichblock the micro-channels. To eliminate this blockage, a bubble-releasingdevice may be used downstream of the pump, or alternatively, theelectrodes may be placed in isolated open reservoirs such that bubblescan escape and the ions cannot invade the flow channel. However, thereservoir housing should be a conductor to enable electric fieldpenetration. The traditional solution to the reaction problem is toreduce the current by using dense packing. Depending on the type ofpacking used, too dense a packing may be undesirable because it cancreate or further aggravate clogging problems.

Because both the low-pressure and electrode reaction disadvantages ofEOPs can be reduced by dense packing within the pump channel,considerable effort has been devoted to fabrication of multiplemicro-channels by lithography or internal packing with high surfacecharge density that still allows electroosmotic flow. One strategy is topack the pump channel with small particles.

An attempt at this is shown in FIG. 1, which illustrates a portion ofconventional micro-pump 100. The conventional pump 100 is formed in asubstrate 102. The substrate has a channel 104 that includes an inlet106 and an outlet 108. An electrolyte flows through the inlet past apacking 110 to the outlet 108. The packing 110 is made of a plurality ofmicro-beads 112. The micro-beads 112 are packed into the channel 104through the inlet 106. The channel 104 further includes a filter 114that holds the micro-beads 112 together as the packing 110 because theopening of the filter 114 has a dimension smaller than the length of thediameter of the micro-beads 112.

The presence of the micro-beads 112 increases the pressure in thechannel 104, which assists in the operation of the pump 100, asdescribed above. However, in addition to clogging problems that a densepacking can create, the installation of the micro-beads 112 isoftentimes extremely tedious, time-consuming and expensive.

In other conventional pumps, a high pressure is created by etching smallchannels into a substrate. Etched channels can reach dimensions on themicrometer scale, but the etching process is also oftentimes tedious andexpensive. Further, a simply-etched channel would not contain a porousmaterial. Thus, several etched channels may need to be formed in asubstrate to achieve optimal pressure in the pump. Repeating the etchingprocess directly affects the key metrics of the manufacturing process,i.e., time and cost.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a prior art micro-pump withmicro-bead packing.

FIG. 2 is a schematic diagram of an example integrated micro-pump andelectro-spray.

FIG. 3 is a photograph of a magnified example monolithic matrix in anexample capillary.

FIG. 4 is a graph plotting pump curves (pressure versus flow rate) forthe example micro-pump of FIG. 1 at different voltages usingacetonitrile as the pumping fluid.

FIG. 5 is a photograph of a magnified Taylor cone emitting from theexample electro-spray of FIG. 1.

FIG. 6 is a schematic diagram of the example integrated micro-pump andelectro-spray as a front-end to a mass spectrometer.

FIG. 7 is an example mass spectrum of example amino acid peaks generatedby the example mass spectrometer with front-end integrated micro-pumpand electro-spray of FIG. 6

DETAILED DESCRIPTION

An example micro-pump of the illustrated examples includes a substratethat has at least one channel, and the substrate integrates a micro-pumpand electro-spray. Further, the example apparatus includes a porousmatrix that is formed from a chemical process, as described herein.

FIG. 2 is a schematic diagram of an example analytical apparatus 200,which generally includes a micro-pump 210 and an electro-spray 212, asdescribed in greater detail below. The analytical apparatus 200 may beutilized in a μ-TAS as described below. The analytical apparatus 200includes a substrate 202 through which at least one channel 204 extends.The substrate 202 may be formed of any suitable material, including, forexample, an inexpensive material such as fused silica. The channel 204has an inlet 206 and an outlet 208. The micro-pump 210 is coupled to thechannel 204 toward or at the inlet 206, and the electro-spray 212 iscoupled to the outlet 208. In some example designs, the micro-pump 210and electro-spray 212 may occupy distinct portions of the substrate 202or, as illustrated in FIG. 2, the micro-pump 210 and electro-spray 212may overlap. Fluid such as, for example, a solvent, electrolyte orbiological sample flow through the channel 204.

The micro-pump 210 includes a power supply 214, which may include, forinstance, batteries and micro-amplifiers, and wires 216 that connect thepower supply to electrodes 218, 219. The electrodes 218, 219 are coupledto the substrate 202, either directly, via reservoirs or othermaterials, as described in greater detail below. In the examplemicro-pump 210, which operates as an electroosmotic micro-pump, thepower supply 214 provides a high voltage and a direct current (DC). Thepower supply 214 is used to create an electric field across thesubstrate 202. The walls 220 of the channel or capillary 204 haveelectric charges, and an electric double layer of counter ionsspontaneously forms at the walls 220, where the counter ions may bedriven by the power supply. When the tangential electric field isapplied, ions in the double layer suffer a Coulombic force, called theMaxwell force, and move toward the electrode of opposite polarity. Thiscreates motion in the fluid near the walls 220. The motion at the walls220 transfers momentum via viscous forces into the bulk of the fluid inthe channel 204, creating flow from inlet 206 to outlet 208.

The illustrated electroosmotic micro-pump 210 has no moving parts and isadvantageously relatively inexpensive to manufacture. Accordingly, ifdesired, the electroosmotic micro-pump 210 may be disposable with therest of the analytical apparatus 200.

Further, because the fluid in the channel 204 is charged, the flow fromthe micro-pump 210, driven by the applied electric field, carries mostof the current. Consequently, the flow rate and current are stronglycorrelated. Precise flow control can be achieved with a simple currentor voltage-controlled circuit (not shown). In addition, for the examplemicro-pump 210, the flow carried current (convective current) may exceedthe usual current due the applied electric field.

The channel 204 of the micro-pump 210 also include a packing such as amatrix 222 that, in addition to overcoming low pressure and chemicalreactions at the electrodes in the channel 204, separates and furthertransports the fluid sample. In this example, the matrix 222 that mayoccupy up to two-thirds of the channel 204, but it will be appreciatedthat the matrix 222 may occupy any percentage of the channel 204 asdesired. The skeleton or matrix 222 may be, for example, a monolithicmatrix and/or a silica-based matrix. Silica has an intrinsic ability togenerate a strong electroosmotic flow due to the presence of ionizablesilanol groups at the surface of the matrix 222. In fact, a silicamonolith matrix has a bimodal pore distribution whose nano-porousstructure, which as discussed in more detail below, produces a highercharge density than regular fused-silica glasses, i.e., the substrate202 alone, or non-porous silica particles. The silanol groups at thefused-silica capillary walls 220 can be easily cross-linked to thematrix 222 to assure secure linkage. Thus, support structures, such asfrits, are unnecessary to hold the matrix 222 in place. Because fritsmay cause pressure drops to occur, the efficiency of the micro-pump 210increases with the use of the matrix 222 and the absence of frits.

It may be desirable to have high pressure and large flow rate in thechannel 204. These metrics are competing principles because the highhydrodynamic resistance offered by a small pore size is responsible forhigh pressure, while large pore-size with large cross-sectional areas isdesirable for a large flow rate. The example analytical apparatus 200uses a bundle of parallel micro-channels with small pore size tooptimize performance based on the competing principles. However, thepore size should not be smaller than the double layer thickness, aspolarization, Maxwell force and flow would all diminish significantly.Hence, an example advantageous structure is a porous medium withparallel pores whose radius is comparable to the double layer thickness.In fact, one optimum channel dimension is roughly the double layerthickness of the pumping fluid, which ranges from 10 nanometers to 1micron. At this dimension, the fluid within the channel is fully chargedwith counter-ions up to its maximum capacitance. The matrix 222 offerssuch a structure with a small pore radius that approaches the doublelayer thickness of some polar organic liquids

In an exemplary embodiment, the matrix 222 is formed by a chemicalprocess such as, for example, a sol-gel process. To form the matrix 222,it may first be desirable to clean the capillary 204. To that end, thefused-silica capillary 204 may be flushed with a cleansing agent suchas, for example, acetone and then baked to remove all liquids inside.This pretreatment substantially eliminates impurities inside thecapillary 204. After, or despite a cleansing, a chemical mixture is theninserted into the channel 204. In one example, the mixture may include0.5 mL of 0.01 M acetic acid, 54 mg of polyethylene glycol and 0.2 mL oftetramethoxysilane that are mixed in a micro-liter size vial bottle andstirred for about 30 minutes in an ice-water bath (0° C.). The matrixpore size can be controlled by adjusting the composition of thesolution. In some cases, sub-micron silica beads are inserted in thesolution to promote subsequent precipitation of more beads and tocontrol the size of the pore size. When all the polyethylene glycol isdissolved and a transparent single-phased solution is observed, thesolution is then introduced inside the channel 204. Then mixture is thenheated. Eventually, the heated mixture transforms, at least in part,into silica precipitate. The precipitated beads are fused together bythe heat. An example heating process includes heating thesolution-filled channel 204 in an oven at 40° C. for 12 hours. Then thetemperature is increased from 40° C. to 300° C. at a rate of 1°C./minute, soaking the capillary 204 for 4 hours at each of 80°, 120°,180°, and 300° C. Finally, the capillary 204, with the silicaprecipitate, is cooled to room temperature at a rate of 1° C./minute.Accordingly, the crystallization of the silica prepared by the sol-gelprocess forms the continuous matrix 222 that has micrometer-sizedthrough pores 224, the size of which can be adjusted by the synthesisprocedure from approximately 10 nanometers to approximately 10 microns.This range is approximately equal to the double layer thickness of manysolvents. The matrix 222 also has nano-porous surfaces 226 (FIG. 3). Inthis embodiment, the matrix 222 is naturally coupled to the walls 220 ofthe capillary 204. The silica-based matrix 222 is generally superior topolymeric monoliths in its mechanical strength and high stability inboth aqueous and organic solutions.

The surface charge of the matrix 222 and/or the dimension of themicro-pores 224 and nano-pores 226 can be adjusted by chemicallyfunctionalizing the surface through silica chemistry, i.e., by adjustingthe composition of the sol-gel solution during synthesis. Thus, thestructure of the matrix 222 can be adjusted without additionalequipment. This allows for easy adjustments to meet special requirementssuch as at low pH conditions. It also allows the matrix to act as achromatograph packing or a catalytic surface.

Because of the disassociation of silanol groups on the nano-porousmatrix 222, the surface of the matrix 222 has high charge density. Thischarge density, in combination with the low conductivity andmicrometer-sized pores 224 of the matrix 222, result in largehydrodynamic resistance. Thus, the matrices 222 are ideal forelectroosmotic micro-pumps, such as the micro-pump 210. FIG. 3illustrates one example of the structure of the resultant matrix 222formed by the above example process. As shown in FIG. 3, the illustratedmatrix 222 is a very porous structure, both in terms of the micro-pores224 between branches of the matrix 222 and the nano-pores 226 on thesurface of the matrix 222. These pores range anywhere from about 10nanometers to 10 microns in width; however, the pores may be larger orsmaller depending upon the desired application.

The analytical apparatus 200 may also include a nonpermeable membranesuch as, for example, a NAFION® membrane 224, at the downstreamelectrode reservoir 219 as shown in FIG. 2. In the illustrated exampleof FIG. 2, the NAFION® membrane 224 is used with the cathode. In otherexamples, the NAFION® membrane 224 may be used with both electrodes 218,219. The NAFION® membrane 224 is a conduction membrane but, in thisembodiment, is not permeable to fluid flow. Thus, the cathode ishydrodynamically isolated from the pump channel 204 such that there isno flow exchange between the electrode reservoir 219 and the channel204. The NAFION® membrane 224 hence offers even more hydrodynamicresistance and further enhances pump pressure.

The NAFION® membrane 224 allows the electric field and specific ions topenetrate but not the ions responsible for electro-chemical reactions atthe electrode 219. As a result, a large voltage (e.g., greater thanseveral kilovolts) can be applied through the capillary 204 of thematrix 222 without producing or introducing electrolytic bubbles or ionsin the capillary 204. Thus, in addition to minimizing fluid leakage andpressure loss, the ion-specific NAFION® membrane 224 minimizes bubblegeneration. Bubbles may be disadvantageous where they block themicro-channels 224 and/or contaminate the sample. Ions also have thepotential to contaminate the matrix 222. Although there may benegligible bubble generation because of the low current through thelow-conducting matrix 222, i.e., the minimum current of less than 100 μAhas a reduced bubble generation to such an extent that any bubbles woulddissolve in the fluid. Further, because the NAFION® membrane 224 isimpermeable to fluid flow including ions responsible forelectro-chemical reactions, the NAFION® membrane 224 also minimizes theproblems caused by pH generation at the electrode 219.

As described above, high pressure is desirable and the examplemicro-pump 210 is capable of sustaining high pressures. In fact, in oneexample, the micro-pump 210 can sustain pressures greater than 4atmospheres, depending upon the fluid use as a sample, while maintainingprecise low flow rates such as, for example, less than amicroliter/minute. The low flow rate allows the micro-pump 210 tosuccessfully operate with small samples. Pressure as high as severalatmospheres may be achieved within a 100 micron capillary 203. A maximumpressure exceeding 20 atmospheres may be achieved with largercapillaries and the smallest through pores 224.

FIG. 4 illustrates an exemplary pump curve for the DC electroosmoticmicro-pump 210 of FIG. 2 at different voltages and with acetonitrile asthe pumping fluid. Organic solvents like methanol, ethanol, and acetonemay also be used. Low-conductivity electrolytes such as, for example,de-ionized water can also be used. It can be seen from the curve thatthe micro-pump 210 with the matrix 222 can generate pressure as high asapproximately 1.2 atmospheres when a potential of 6 kV is applied andacetonitrile is used as the test fluid. Thus, the electroosmoticmicro-pump 210 with the matrix 222, with its high pressure and lowcurrent, is ideal to dive flow against large loads in micro-systems suchas μ-LC, μ-FIA, and micro-chip sensors. Other pressures are achievablewhen other fluids are used in the channel 204, depending on theproperties of the fluid sample used.

Returning to FIG. 2, the outlet 208 of the channel 204 is coupled to anelectro-spray 212. The electro-spray 212, or nano-spray, generates smallions or droplets 230 that are easily ionized over a broad range of flowrates for any general sample. For example, the electro-spray 212 mayproduce a Taylor cone 228, which is a cone of fluid that emits the smallcharged droplets 230. Multiple Taylor cones may form at the outlet 208if there are multiple paths through the matrix 222. An example Taylorcone 228 is shown in FIG. 5. The electro-spray 212 is able to form thestable Taylor cone 228 because of the high pressure the micro-pump 210can deliver. Further, in this embodiment, the micro-pump 210 canmaintain these high pressures with less than a 100 micro-liter sample.In addition the integration of a DC micro-pump with the matrix 222 intothe device 200 with the electro-spray 212 allows for highly controllablesample flow-rates at as little as approximately a pico-liter per second.This allows easy sample delivery of small samples from the substrate 202to another analytical device such as, for example, a mass spectrometer,or any other suitable device that could not be integrated into the samesubstrate 202, which is discussed in more detail below.

The use of the porous matrix 222 in combination with the electro-spray212 may have several distinct advantages over most commerciallyavailable nano-sprays that were designed specifically to process smallsample volumes. The multiplicity of flow paths in the matrix 222 resultsin fewer clogging problems even when used with organic or normal-phasesamples, an issue that plagues most existing nano-sprays. Other benefitshave been described herein such as, for example, the ability to pump andspray normal-phase sample, such as organic fluids.

There is a focused electric field at the Taylor cone 228 that causescharges (typically ions of the same polarity as the walls 220 at theoutlet 208) to concentrate at the tip of the Taylor cone 228. When thecharge density becomes excessive, sub-micron charged droplets 230 areemitted from the Taylor cone 228. With evaporation of the solvent inflight, the charge density of the droplets 230 increases because thesolvent within the droplet 230 evaporates but the droplet 230 remainscharged. Because the volume of the droplet 230 decreases rapidly, thesurface tension of the droplet 230 is unable to oppose the electrostaticrepulsive forces of the charges within the droplet 230. This causes thedroplet 230 to explode into many smaller droplets 230. This is known asRayleigh fission. The final droplets 230 are nanometer in dimension andcontains charged (ionized) molecules that will be identified in anyadjoined μ-TAS. In FIG. 6, the example adjoined μ-TAS is a massspectrometer 300. The electro-spray 212 may be used as a front-end orinterface with many other μ-TAS or other analytical devices as wellincluding, for example, biochips, diagnostic equipment, an implantabledrug delivery device, a circuit cooling device, a device used formicro-fuel cell applications, and/or a capillary electrophoresischromatograph.

Referring now to FIG. 6, mass spectrometers are commonly known,particularly for use with the detection of trace quantities ofcontaminants or other toxins, and will not be discussed here in greatdetail. However, in brief: in the mass spectrometer 300 of FIG. 6, thedroplets 230 formed by the analytical apparatus 200 accelerate throughan ion analyzer 302, which in this example is a quadruple ion analyzer302. The ion analyzer 302 uses positive and negative voltages to controlthe paths of the droplets 230. The droplets 230 travel down the pathbased on their mass to charge ratio; therefore, the path of a droplet230 will depend on its mass. The droplet 230 eventually hits a detector304. The detector 304 works by producing an electric signal when struckby a charged droplet 230. The detector 304 determines which droplets 230have struck the detector 304 and a spectrum is produced. An examplespectrum is shown in FIG. 7, which accurately identifies peptide andamino acids.

To generate a cone 228 that can be used as a front-end to a massspectrometer, considerable pressure typically needs to be sustained atthe orifice where the cone 228 is situated. This usually requires large,expensive pumps. However, as described above, the micro-pump 210 withthe matrix 222 is capable of producing and sustaining adequate highpressure for the electro-spray 212 to be properly used as the front-endof the mass spectrometer 300. Further, the micro-pump 210 is integratedwith the electro-spray 212 together forming a analytical apparatus thatis cheap to manufacture, disposable so it does not need to be cleaned orsterilized and portable so it can be used in the field.

Although certain example methods, apparatus and articles of manufacturehave been described herein, the scope of coverage of this patent is notlimited thereto. On the contrary, this patent covers all methods,apparatus and articles of manufacture fairly falling within the scope ofthe appended claims either literally or under the doctrine ofequivalents.

1. A micro-pump comprising: a substrate having at least one channel,wherein the channel has an inlet and an outlet; a first and secondelectrode coupled to the substrate, wherein the electrodes deliver acurrent that produces an electric field across the substrate to create aflow from the inlet to the outlet of a fluid contained in the channel;and at least a portion of the channel contains a chemically formedporous matrix.
 2. The micro-pump as defined in claim 1, wherein thematrix is formed from a sol-gel chemical process.
 3. The micro-pump asdefined in claim 1, wherein the matrix is formed by fusing nano-porousbeads.
 4. The micro-pump as defined in claim 1, wherein the matrix is atleast one of monolithic or formed from a silica precipitate.
 5. Themicro-pump as defined in claim 1, wherein matrix has a plurality ofpores.
 6. The micro-pump as defined in claim 1, wherein the matrix hascharged surfaces.
 7. The micro-pump as defined in claim 1, wherein themicro-pump is used in a total analytical system.
 8. The micro-pump asdefined in claim 7, wherein the total analytical system is at least oneof: a mass spectrometer, a biochip, a diagnostic equipment, animplantable drug delivery device, a circuit cooling device, a deviceused for micro-fuel cell applications, or a capillary electrophoresischromatograph.
 9. The micro-pump as defined in claim 1, furthercomprising at least one electrode that is coupled to a conductingmembrane that blocks ion responsible for electro-chemical reactions atthe electrode.
 10. The micro-pump as defined in claim 9, wherein themembrane minimizes bubbles in the at least one channel.
 11. Themicro-pump as defined in claim 1, wherein the micro-pump is coupled toan electro-spray forming a combination integrated with the substrate,wherein the electro-spray emits the fluid from the at least one channel.12. The micro-pump as defined in claim 11, wherein the combination isone of at least disposable or portable.
 13. The micro-pump as defined inclaim 11, wherein the combination sustains a high pressure.
 14. Themicro-pump as defined in claim 11, wherein the combination maintainsprecise low flow rates.
 15. The micro-pump as defined in claim 11,wherein the fluid is emitted from the at least one channel via a Taylorcone.
 16. The micro-pump as defined in claim 11, wherein theelectro-spray may operate with less than 100 micro-liter samples. 17.The micro-pump as defined in claim 11, wherein the fluid is an organicmaterial.
 18. A method of creating a porous matrix in a channel in asubstrate for use in an integrated micro-pump and electro-spray, themethod comprising: inserting a chemical mixture into at least a portionof the channel; inserting silica beads to control precipitated bead andpore size; heating the mixture until a precipitate forms; and coolingthe channel and the precipitate.
 19. The method as defined in claim 18,wherein the precipitate forms a monolithic matrix.
 20. The method asdefined in claim 18, wherein the mixture is formed from a sol-gelprocess.
 21. The method as defined in claim 18, wherein the matrix issilica precipitate.
 22. The method as defined in claim 18, wherein thechannel is cleaned before the mixture is inserted.
 23. The method asdefined in claim 18, wherein the matrix forms micro-pores.
 24. Themethod as defined in claim 18, wherein the surface of the matrix hasnano-pores.
 25. The method as defined in claim 18, wherein the matrixmay be used in at least one of aqueous and organic solutions.
 26. Ameans of creating a porous matrix for use in an integrated micro-pumpand electro-spray, the means including: means for forming a chemicalmixture; means for inserting the chemical mixture into at least aportion of a channel formed in a substrate; means for heating themixture until a precipitate forms; and means cooling the channel and theprecipitate.